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PMID: 7676810 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients.

Acta neuropathologica ·Vol. 89 ·No. 6 ·1995-00-00 ·Pages 544-51

Huell M, Strauss S, Volk B, Berger M, Bauer J

Abstract

Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD) and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this study, we investigated the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Using the Bielschowsky silver-staining method, we were able to differentiate between four types of plaques described earlier: diffuse, primitive, classic and compact. While diffuse plaques represent the early stage of plaque formation, primitive and classic plaques are thought to represent later stages of plaque development. We investigated serial sections of paraffin-embedded cortices of ten clinically diagnosed and histopathologically confirmed AD patients and ten patients with no clinical history of dementia. We found plaques in the brains of both nondemented and demented persons using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the group of clinically nondemented persons, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger portion of lesions in the group of AD brains. IL-6 could not be detected in plaques of patients without dementia. Many IL-6-positive plaques were found in six of the AD brains and to a smaller extent in the other four AD cases. In the six cases with a large number of IL-6-positive plaques, IL-6 was found in a significantly higher ratio of diffuse plaques than expected from a random distribution of IL-6 in all plaque types.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms
Aged Aged, 80 and over Alzheimer Disease/metabolism,pathology Brain/pathology Brain Chemistry Humans Immunohistochemistry Interleukin-6/metabolism Middle Aged Silver Staining
Chemicals
Interleukin-6
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Huell M
Department of Psychiatry, Freiburg University Medical School, Germany.
Strauss S
Volk B
Berger M
Bauer J
References (52)
52 references, click to expand
  1. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
    Ann Neurol. 1991 Oct;30(4):572-80 PMID: 1789684
  2. Temporal sequence of plaque formation in the cerebral cortex of non-demented individuals.
    J Neuropathol Exp Neurol. 1993 Mar;52(2):135-42 PMID: 8440995
  3. Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices.
    FEBS Lett. 1991 Jul 8;285(1):111-4 PMID: 1712317
  4. Ultrastructure of diffuse plaques in senile dementia of the Alzheimer type: comparison with primitive plaques.
    Acta Neuropathol. 1991;82(1):13-20 PMID: 1950474
  5. Interleukin-6 and selected plasma proteins in healthy persons of different ages.
    Neurobiol Aging. 1994 Nov-Dec;15(6):771-2 PMID: 7534383
  6. Diagnosis of Alzheimer's disease.
    Arch Neurol. 1985 Nov;42(11):1097-105 PMID: 2864910
  7. A special type of senile plaque, possibly an initial stage.
    Acta Neuropathol. 1987;74(2):133-41 PMID: 3673504
  8. Senile plaques do not progressively accumulate with normal aging.
    Acta Neuropathol. 1994;87(5):520-5 PMID: 8059605
  9. Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system.
    Clin Immunol Immunopathol. 1990 Nov;57(2):233-41 PMID: 2208805
  10. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6.
    Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10061-5 PMID: 7694279
  11. Distinctive, rapid, and easy labeling of diffuse plaques in the Alzheimer brains by a new methenamine silver stain.
    Acta Neuropathol. 1990;79(5):569-72 PMID: 1691573
  12. Interleukin-6 and its receptor during homeostasis, inflammation, and tumor growth.
    Klin Wochenschr. 1989 Jul 17;67(14):697-706 PMID: 2504990
  13. Regulation of interleukin-6 (IL-6) secretion in primary cultured rat astrocytes: synergism of interleukin-1 (IL-1) and pituitary adenylate cyclase activating polypeptide (PACAP).
    Brain Res. 1994 Feb 21;637(1-2):197-203 PMID: 7910101
  14. Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.
    Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7552-6 PMID: 1652752
  15. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity.
    Ann Neurol. 1990 May;27(5):457-64 PMID: 2360787
  16. Interleukin-6 in clinical medicine.
    Ann Hematol. 1991 Jun;62(6):203-10 PMID: 1854882
  17. Distribution pattern and functional state of alpha 1-antichymotrypsin in plaques and vascular amyloid in Alzheimer's disease. A immunohistochemical study with monoclonal antibodies against native and inactivated alpha 1-antichymotrypsin.
    Acta Neuropathol. 1991;82(3):200-7 PMID: 1927277
  18. Subtypes and differential laminar distributions of beta A4 deposits in Alzheimer's disease: relationship with the intellectual status of 26 cases.
    Acta Neuropathol. 1991;81(3):328-35 PMID: 1711758
  19. Early senile plaques in Alzheimer's disease demonstrated by histochemistry, immunocytochemistry, and electron microscopy.
    Hum Pathol. 1990 Dec;21(12):1221-6 PMID: 2249835
  20. Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2-macroglobulin and C-reactive protein.
    Brain Res. 1993 Dec 3;629(2):245-52 PMID: 7509248
  21. Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid.
    J Neuroimmunol. 1989 Jul;23(2):109-16 PMID: 2656753
  22. Cytokines in Alzheimer's disease.
    Prog Neuropsychopharmacol Biol Psychiatry. 1991;15(4):481-95 PMID: 1749826
  23. Pathological markers associated with normal aging and dementia in the elderly.
    Ann Neurol. 1993 Oct;34(4):566-73 PMID: 8215244
  24. Morphology and distribution of plaque and related deposits in the brains of Alzheimer's disease and control cases. An immunohistochemical study using amyloid beta-protein antibody.
    Lab Invest. 1989 Jan;60(1):113-22 PMID: 2642985
  25. Analysis of staining methods for different cortical plaques in Alzheimer's disease.
    Acta Neuropathol. 1994;87(2):174-86 PMID: 7513488
  26. Complement gene expression in neuroblastoma and astrocytoma cell lines of human origin.
    Neurosci Lett. 1993 Jul 9;157(1):99-102 PMID: 8233040
  27. Neuropathological stageing of Alzheimer-related changes.
    Acta Neuropathol. 1991;82(4):239-59 PMID: 1759558
  28. Beta-amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer's disease.
    Brain Res. 1992 Jan 8;569(1):141-5 PMID: 1611474
  29. A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer's neurofibrillary tangles.
    Neuropathol Appl Neurobiol. 1986 Jan-Feb;12(1):3-9 PMID: 2422580
  30. Inflammatory mechanisms in Alzheimer's disease: implications for therapy.
    Am J Psychiatry. 1994 Aug;151(8):1105-13 PMID: 7518651
  31. Acute phase proteins are present in amorphous plaques in the cerebral but not in the cerebellar cortex of patients with Alzheimer's disease.
    Neurosci Lett. 1990 Oct 30;119(1):75-8 PMID: 1711182
  32. Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients.
    Lab Invest. 1992 Feb;66(2):223-30 PMID: 1370967
  33. Diffuse plaques do not accentuate synapse loss in Alzheimer's disease.
    Am J Pathol. 1990 Dec;137(6):1293-7 PMID: 2124413
  34. Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease.
    Acta Neuropathol. 1989;78(4):337-47 PMID: 2551122
  35. The viral hypothesis of Alzheimer's disease. Absence of antibodies to lentiviruses.
    Arch Neurol. 1990 Feb;47(2):177-8 PMID: 2302089
  36. Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor.
    J Neuroimmunol. 1993 Jun;45(1-2):163-73 PMID: 8392518
  37. Comparison of four staining methods on the detection of neuritic plaques.
    Acta Neuropathol. 1989;78(1):22-7 PMID: 2472039
  38. Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain.
    Eur J Neurosci. 1993 Nov 1;5(11):1426-35 PMID: 8287192
  39. Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older.
    Arch Neurol. 1993 Apr;50(4):349-58 PMID: 8460956
  40. Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer's and Parkinson's disease patients.
    Neurosci Lett. 1993 Nov 12;162(1-2):179-82 PMID: 8121624
  41. Alzheimer patients and Down patients: abnormal presynaptic terminals are related to cerebral preamyloid deposits.
    Neurosci Lett. 1990 Oct 30;119(1):56-9 PMID: 1965862
  42. Excitatory amino acids and Alzheimer's disease.
    Neurobiol Aging. 1989 Sep-Oct;10(5):593-602 PMID: 2554168
  43. Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells.
    Brain Res. 1993 Jan 22;601(1-2):88-94 PMID: 8431789
  44. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection.
    J Immunol. 1989 Feb 1;142(3):948-53 PMID: 2536416
  45. A4 protein in Alzheimer's disease: primary and secondary cellular events in extracellular amyloid deposition.
    J Neuropathol Exp Neurol. 1989 Nov;48(6):674-91 PMID: 2677252
  46. Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease.
    Cell. 1988 Feb 26;52(4):487-501 PMID: 3257719
  47. Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists.
    Arch Pathol Lab Med. 1993 Feb;117(2):132-44 PMID: 8427562
  48. Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease.
    J Neurol Neurosurg Psychiatry. 1994 Apr;57(4):419-25 PMID: 8163989
  49. The acute phase response.
    Immunol Today. 1994 Feb;15(2):74-80 PMID: 7512342
  50. Expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) mRNAs in rat brain during postnatal development.
    Brain Res. 1994 Feb 21;637(1-2):10-4 PMID: 8180786
  51. Activation of the classical complement pathway in brain tissue of Alzheimer patients.
    Neurosci Lett. 1989 Dec 15;107(1-3):341-6 PMID: 2559373
  52. Interleukin-6: a cytokine for gerontologists.
    J Am Geriatr Soc. 1993 Feb;41(2):176-81 PMID: 8426042
Article Info
Journal
Acta neuropathologica
Abbr.
Acta Neuropathol
ISSN
0001-6322
Published
1995-00-00
Pages
544-51
Language
English
Region
Germany
NLM ID
0412041
Subset
IM
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